What Really Caused the Deadly Plague of Athens?

In the summer of 430 B.C., a mysterious epidemic swept through Athens. Victims developed raging fevers, inflamed eyes, vomiting and violent diarrhea. Some suffered delirium and memory loss, while others broke out in sores and pustules. Many died within days.

The disease returned in successive waves, with estimates suggesting it killed between a quarter and a third of Athens’ population, including its influential general Pericles. Thucydides was one of the lucky ones. The Greek historian survived the epidemic and left behind a vivid eyewitness account that has baffled scholars for centuries, inspiring theories ranging from smallpox, typhoid fever and measles to bubonic plague.

Now, nearly 2,500 years later, researchers have proposed an unexpected culprit: an unusually virulent, invasive strain of Salmonella enterica, a bacterium more commonly associated with food poisoning than a deadly plague.

The epidemic struck at a particularly vulnerable moment. Athens was in the second year of the Peloponnesian War, a devastating conflict with its rival Sparta that would help bring an end to the Golden Age of ancient Greece. Rather than confront Sparta’s superior land army, Pericles urged inhabitants of Athens’ surrounding countryside to shelter behind the city’s fortified walls, while relying on its navy to launch attacks by sea. Tens of thousands poured into Athens, many finding shelter in temples, public spaces and makeshift dwellings. 

But the strategy designed to protect Athenians from Spartan forces might have left the city vulnerable to a different threat. “Wartime Athens was close to a perfect setting for this disease,” says Christina-Maria Trakatelli, an associate professor of internal medicine at Aristotle University of Thessaloniki and lead author of the new study.

Trakatelli argues that the city’s swollen population could have facilitated the spread of Salmonella enterica, while the harsh conditions of wartime life might have increased the risk of life-threatening illness. “Malnutrition, crowding and poor sanitation are the conditions that turn salmonella from a stomach bug into a lethal bloodstream infection,” she says.

The same species of salmonella, Salmonella enterica, that causes ordinary food poisoning can also cause a potentially fatal illness. “The difference is in how the infection behaves,” Trakatelli explains. In healthy people, she says, salmonella usually remains in the intestines, causing a few days of diarrhea. But in people weakened by malnutrition or stress, the bacteria can enter the bloodstream and spread throughout the body.

“That illness looks much more like typhoid than food poisoning,” she says, with high fever, confusion and potentially serious complications affecting multiple organs. Even today, invasive nontyphoidal salmonella can be deadly, with one study putting its estimated fatality rate at roughly 20 percent.

To investigate the cause of the epidemic, Trakatelli and her colleagues revisited Thucydides’ eyewitness account, comparing his descriptions of the disease with the symptoms and spread of various infectious illnesses, while also reviewing earlier archaeological and DNA evidence.

The researchers were particularly intrigued by Thucydides’ description of the fate of scavenging animals. “All the birds and beasts that prey upon human bodies, either abstained from touching them (though there were many lying unburied), or died after tasting them,” he wrote, with dogs providing the clearest example. 

“It is one of the most important clues in the whole account,” Trakatelli says. “A disease that kills animals as well as humans must be able to cross between species. That single detail rules out most of the diseases proposed before.”

Unlike smallpox, typhoid fever and measles, which infect only humans, nontyphoidal Salmonella can infect both humans and animals. Trakatelli also maintains that invasive nontyphoidal salmonella offers the closest match to the other symptoms Thucydides described, including high fever, vomiting, diarrhea and delirium, as well as the epidemic’s high death toll and the apparent immunity of survivors.

The researchers also revisited a 2006 study involving a mass grave in Athens’ Kerameikos cemetery, where archaeologists had uncovered the remains of approximately 150 people hastily buried around the time of the epidemic. Scientists analyzed DNA from three ancient teeth and reported finding the strain of Salmonella enterica responsible for typhoid fever. Tests for other suspected pathogens, including those responsible for bubonic plague and epidemic typhus, were negative.

But other researchers challenged the findings, arguing that the DNA fragments weren’t a convincing match for salmonella and might have come from an unrelated bacterium that contaminated the remains.

Trakatelli acknowledges the limitations of the original DNA tests but argues that they still point to Salmonella enterica, potentially a nontyphoidal strain. “I would treat them as a signal pointing towards salmonella, not as proof of any specific type,” she says.

Yet questions remain about how closely salmonella fits Thucydides’ account. “Nontyphoidal Salmonella as the cause of the Plague of Athens is highly unlikely, both on clinical and epidemiological grounds,” argues Robert J. Littman, a historian at the University of Hawai’i who has studied the epidemic. Littman notes that Thucydides described a pustular rash covering victims’ bodies, a symptom not characteristic of salmonella infections. He also points to Thucydides’ description of a highly contagious disease that spread rapidly through the population, arguing that nontyphoidal Salmonella has a much lower transmission rate than diseases such as smallpox and epidemic typhus.

For all the competing theories, no single pathogen has been conclusively linked to the epidemic. More sophisticated DNA testing of the ancient remains might offer the best chance of settling the debate.